THE RISK MODEL OF DEVELOPING SCHIZOPHRENIA BASED ON TEMPERAMENT AND CHARACTER

Introduction: Cloninger\u27s psychological model of temperament and character confirms that the personality development is influenced by biological and psychological processes. The aim of this study is to examine personality dimensions and to determine which variable separates the healthy from the ill in the best way and could be a possible psychological marker for the presence of the illness. Methods: This research included 152 subjects, 76 patients with schizophrenia and 76 healthy controls, selected on the basis of medical interviews, random population sampling model from a wider social community using the independent T-Tests. The Temperament and Character Inventory (TCI), which compared personality traits of the patients with schizophrenia and the healthy control group, was used. Dependence of variables in these categories was assessed using the Chi-square and Fisher\u27s tests, and the impact of variables on schizophrenia was tested using univariate and multivariate binary logistic regression. The same method was used for making the mathematical model. Results: Unlike the control group, patients with schizophrenia exhibited higher Harm avoidance (HA) and Self - transcendence (ST) scores as well as lower Self - directedness (SD) and Cooperativeness (C) scores. Multivariate binary logistic regression showed that Responsibility, Purposefulness, Resourcefulness, Cooperativeness and Compassion dimensions were significantly more present in the patients with schizophrenia. The new variable Model (area=0.896, p<0.0005) is composed of five TCI parameters. It proved to be a reliable marker for separation the healthy from the ill ones (area=0.896, p<0.0005). It has a good sensitivity (80%) and specificity (84%). Conclusions: Research has emphasized variables in the temperament and character inventory, which are the best markers for distinguishing between the healthy and the ill, thus making the mathematical model

Étude des déterminants de l'interaction entre la glycoprotéine d'enveloppe gp120 du VIH-1 et CCR5

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Different Domains of CD81 Mediate Distinct Stages of Hepatitis C Virus Pseudoparticle Entry

The CD81 tetraspanin was first identified as a hepatitis C virus (HCV) receptor by its ability to bind the soluble ectodomain of envelope glycoprotein E2 (sE2). More recently, it has been suggested that CD81 is necessary but not sufficient for HCV entry into target cells. Here we present further evidence that putative human hepatocyte-specific factors act in concert with CD81 to mediate sE2 binding and HCV pseudoparticle (HCVpp) entry. Moreover, we show that CD81-mediated HCVpp entry entails E2 binding to residues in the large extracellular loop as well as molecular events mediated by the transmembrane and intracellular domains of CD81. The concept that CD81 receptor function progresses in stages is further supported by our finding that anti-CD81 monoclonal antibodies inhibit HCVpp entry by different mechanisms. The half-life of CD81-HCVpp binding was determined to be approximately 17 min, and we propose that binding is followed by CD81 oligomerization, partitioning into cholesterol-rich membrane domains, or other, lateral protein-protein interactions. This results in the formation of a receptor-virus complex that undergoes endocytosis and pH-dependent membrane fusion

The Crown and Stem of the V3 Loop Play Distinct Roles in Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Interactions with the CCR5 Coreceptor

Human immunodeficiency virus type 1 envelope glycoprotein gp120 interacts with CD4 and the CCR5 coreceptor in order to mediate viral entry. A CD4-induced surface on gp120, primarily composed of residues in the V3 loop and the C4 domain, interacts with CCR5. In the present study, we generated envelope glycoproteins comprising chimeric V3 loops and/or V3 loops with deletions and studied their binding to CCR5 amino-terminal domain (Nt)-based sulfopeptides and cell surface CCR5, as well as their ability to mediate viral entry. We thus delineated two functionally distinct domains of the V3 loop, the V3 stem and the V3 crown. The V3 stem alone mediates soluble gp120 binding to the CCR5 Nt. In contrast, both the V3 stem and crown are required for soluble gp120 binding to cell surface CCR5. Within the context of a virion, however, the V3 crown alone determines coreceptor usage. Our data support a two-site gp120-CCR5 binding model wherein the V3 crown and stem interact with distinct regions of CCR5 in order to mediate viral entry

Etude de la fonction de claudine-1 dans l'entrée du virus de l'hépatite C

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Hepatitis C Virus Entry Requires a Critical Postinternalization Step and Delivery to Early Endosomes via Clathrin-Coated Vesicles

Hepatitis C virus (HCV) is a major human pathogen associated with life-threatening liver disease. Entry into hepatocytes requires CD81 and a putative second receptor. In this study, we elucidated the postreceptor attachment stages of HCV entry using HCV pseudoparticles (HCVpp) as a model system. By means of dominant-negative mutants and short interfering RNAs of various cellular proteins, we showed that HCVpp enter via clathrin-coated vesicles and require delivery to early but not to late endosomes. However, the kinetics of HCV envelope glycoprotein-mediated fusion are delayed compared to those of other viruses that enter in early endosomes. Entry of HCVpp can be efficiently blocked by bafilomycin A1, which neutralizes the pH in early endosomes and impairs progression of endocytosis beyond this stage. However, low-pH exposure of bafilomycin A1-treated target cells does not induce entry of HCVpp at the plasma membrane or in the early stages of endocytosis. These observations indicate that, subsequent to internalization, HCVpp entry necessitates additional, low-pH-dependent interactions, modifications, or trafficking, and that these events are irreversibly disrupted by bafilomycin A1 treatment

CCR5 and CXCR4 Usage by Non-Clade B Human Immunodeficiency Virus Type 1 Primary Isolates

CCR5 and CXCR4 usage has been studied extensively with a variety of clade B human immunodeficiency virus type 1 (HIV-1) isolates. The determinants of CCR5 coreceptor function are remarkably consistent, with a region critical for fusion and entry located in the CCR5 amino-terminal domain (Nt). In particular, negatively charged amino acids and sulfated tyrosines in the Nt are essential for gp120 binding to CCR5. The same types of residues are important for CXCR4-mediated viral fusion and entry, but they are dispersed throughout the extracellular domains of CXCR4, and their usage is isolate dependent. Here, we report on the determinants of CCR5 and CXCR4 coreceptor function for a panel of non-clade B isolates that are responsible for the majority of new HIV-1 infections worldwide. Consistent with clade B isolates, CXCR4 usage remains isolate dependent and is determined by the overall content of negatively charged and tyrosine residues. Residues in the Nt of CCR5 that are important for fusion and entry of clade B isolates are also important for the entry of all non-clade B HIV-1 isolates that we tested. Surprisingly, we found that in contrast to clade B isolates, a cluster of residues in the second extracellular loop of CCR5 significantly affects fusion and entry of all non-clade B isolates tested. This points to a different mechanism of CCR5 usage by these viruses and may have important implications for the development of HIV-1 inhibitors that target CCR5 coreceptor function